title: Clinical impact of new prostate-specific antigen WHO standardization on biopsy rates and cancer detection.
abstract: BACKGROUND
  Clinicians may be unaware that replacement of the historical total prostate-specific antigen (tPSA) standard with the WHO 96/670 international standard leads to difficulties in interpreting tPSA results. Our aim was to investigate the relationship between the Hybritech and WHO calibrations of the Beckman Coulter tPSA assay, and to assess the impact on prostate cancer (PCa) detection.
  
  
  METHODS
  tPSA concentrations were measured in 106 serum samples with both Hybritech and WHO calibrations. The established relationships were used for an in silico experiment with a cohort of 5865 men. Differences in prostate biopsy rates, PCa detection, and characteristics of missed cancers were calculated at biopsy thresholds of 3.0 and 4.0 microg/L.
  
  
  RESULTS
  A linear relationship was observed between the 2 calibrations, with a 20.3% decrease in tPSA values with the WHO standard compared with the Hybritech calibration. Applying the WHO calibration to the cohort of 5865 men yielded a 20% or 19% decrease in prostate biopsies and a 19% or 20% decrease in detected cancers compared with the Hybritech calibration, at a cutoff for biopsy of 3.0 or 4.0 microg/L, respectively. The decrease in detected cancers declined to 9% or 11% if an abnormal result in a digital rectal examination or a transrectal ultrasound evaluation was used as trigger for prostate biopsy (cutoff of 3.0 or 4.0 microg/L, respectively).
  
  
  CONCLUSIONS
  Application of the WHO standard for tPSA assays with commonly used tPSA thresholds leads to a significant decrease in PCa detection. Careful assessment of the relationship between the WHO standard and the thresholds used for prostate biopsy is hence necessary.
authors.affiliation: Department of Urology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: F H
authors.initials: FH
authors.lastname: Jansen
authors.forename: M
authors.initials: M
authors.lastname: Roobol
authors.forename: C H
authors.initials: CH
authors.lastname: Bangma
authors.forename: R H N
authors.initials: RH
authors.lastname: van Schaik
mesh_terms: D001706:Biopsy / Q000706:statistics & numerical data; D002138:Calibration; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000097:blood / Q000592:standards*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology; D012015:Reference Standards; D014944:World Health Organization
chemical_list: D017430:Prostate-Specific Antigen